It is known that lupulin, in contradistinction to humulone, has a pronounced retarding action with regard to tubercular bacteria. Isohumulone, which can be prepared by isomerization from humulone, on the other hand, has this tuberculosis retarding property to an even greater extent. Tests in vitro have shown that it is practically just as active as Conteben. However, it is of importance that isohumulone is tolerated without complaints. In addition to this important use, isohumulone can be used as a starting or intermediate product in chemistry.
Another use is in the brewing industry, since isohumulone represents the essential part of so-called hops bitters which are produced in the brewing process from the hops substances upon the so-called wort boiling. This isomerization by boiling takes place at a pH of about 5.5 and proceeds very slowly and incompletely. With a boiling time of up to 2 hours, the yield is at most 30-35%.
It would, therefore, be extremely desirable to be able to convert humulone rapidly and gently, but with high yield, into isohumulone. Since the twenties, it has been known that the isomerization of humulone upon boiling in aqueous alkaline solutions takes place with high speed and with substantially better yields (German Pat. No. 413,913). The isomerization is effected with aqueous soda or sodium hydroxide solution (OH ion concentration 1/10,000 and 1/1000 N respectively) by boiling for 30 minutes or 10 minutes respectively. A similar manner of operation is known from Pet. Journ. d. Brass. 1948, 679. Furthermore, isomerization reactions of humulone in aqueous alkaline carbonate and phosphate buffer solutions having pH values of 8-13 are known (U.S. Pat. Nos. 2,816,032 and 2,647,837 and British Pat. No. 855,401). In the last mentioned British patent it is shown that the isomerization of humulone proceeds with sufficient speed only starting with a pH of 9.0. In Australian Pat. No. 245,941 Hildebrand et al. describe the photochemical isomerization of humulone to isohumulone. The reaction, however, is not suitable for manufacture on a synthetic scale; it consumes a very large amount of energy and leads to uncontrollable secondary reactions.
The known relatively strong alkaline isomerization of humulone to isohumulone has the disadvantage that the conversion can frequently proceed beyond isohumulone to undesired compounds, for instance, humulonic acid. The examination by use of thin-layer chromatography of isohumulone preparations obtained by alkaline isomerization of pure humulone shows that a large number of reaction products are produced whose nature is to the greatest part not yet clarified. In order to obtain a pure isohumulone therefore an expensive purifying operation, such as, for instance, counter-flow distribution is necessary.